A deep learning approach to perform defect classification of freeze-dried product.

Cosmetic inspection of freeze-dried products is an important part of the post-manufacturing quality control process. Traditionally done by human visual inspection, this method poses typical challenges and shortcomings that can be addressed with innovative techniques. While many cosmetic defects can occur, some are considered more critical than others as they can be harmful to the patient or affect the drug's efficacy.

Exploring the Experiences of Times Without Care and Encounters in Persons With Dementia in the Swiss and German Nursing Home and Domiciliary Care Settings: Protocol for an Ethnographic Multimethods Study.

Background: Persons with dementia spend a large part of the day without care and encounters, often without activity, as confirmed by numerous studies. However, no scientific analysis has examined how persons with dementia experience these periods. Such knowledge would be highly relevant for health care professionals and relatives to develop adequate strategies for dealing with times without care.

Optimization of continuous spin-freeze-drying: The role of spin-freezing on quality attributes and drying efficiency of a model peptide formulation.

Continuous spin-freeze-drying is an innovative pharmaceutical manufacturing approach offering real-time monitoring and control at the individual vial level, unlike conventional batch lyophilization. A central feature of this technology is spin-freezing, which involves rapidly spinning liquid-filled vials under a precisely controlled cold gas flow, resulting in a thin, uniform frozen product layer. Using a model peptide formulation, we investigated the impact of different cooling and crystallization rates on quality attributes (QA) and primary drying duration.

Investigating screw-agitator speed ratio impact on feeding performance in pharmaceutical manufacturing using discrete element method.

In continuous powder handling processes, precise and consistent feeding is crucial for ensuring the quality of the final product. The intermixing effect caused by agitators, which alters the powder's bulk density, flow rate, and flow patterns, plays a significant role in this process, yet it is often overlooked. This study combines discrete element method (DEM) modeling and experiments using a commercial-scale feeder to propose a Digital Twin (DT) framework.

The influence of thermal radiation during microwave-assisted freeze-drying of pharmaceutical unit doses.

New drying technologies for biologicals have recently been developed to accelerate the time-consuming batch freeze-drying (BFD) process. Among others, microwave-assisted freeze-drying (MFD) has been suggested as a faster and more effective drying technology. In this study, MFD cycles with the microwave radiation switched on and off were performed to assess the contribution of the microwave radiation to drying acceleration.

Automated particle inspection of continuously freeze-dried products using computer vision.

The pharmaceutical industry is progressing towards more continuous manufacturing techniques. To dry biopharmaceuticals, continuous freeze drying has several advantages on manufacturing and process analytical control compared to batch freeze-drying, including better visual inspection potential. Visual inspection of every freeze-dried product is a key quality assessment after the lyophilization process to ensure that freeze-dried products are free from foreign particles and defects.

Optimizing the secondary drying phase of a continuous Spin-Freeze Drying process: A semi-mechanistic modelling approach.

Over the past decade, continuous spin freeze-drying technology has emerged as a promising alternative to conventional batch freeze-drying, effectively addressing many of the latter's inherent disadvantages. Much of the focus during this period has been on controlling and optimizing the primary drying phase of this process. However, optimizing the secondary drying step is equally critical for the overall efficiency of the process.

Recruiting Persons With Dementia: A Systematic Review of Facilitators, Barriers, and Strategies.

Study recruitment of persons with dementia is challenging. We aimed to assess facilitators, barriers, and strategies to identify and approach persons with dementia for recruitment to dementia care studies. We systematically searched MEDLINE/PubMed, CINAHL, Web of Science, and other sources (ORRCA [Online Resource for Research in Clinical triAls]; pertinent evidence syntheses; citation searching) and narratively summarised the results (PROSPERO CRD42022342600).

Hybrid modeling of T-shaped partial least squares regression and transfer learning for formulation and manufacturing process development of new drug products.

T-shaped partial least squares regression (T-PLSR) is a valuable machine learning technique for the formulation and manufacturing process development of new drug products. An accurate T-PLSR model requires experimental data with multiple formulations and process conditions. However, it is usually challenging to collect comprehensive experimental data using large-scale manufacturing equipment because of the cost, time, and large consumption of raw materials.

DCAF15 control of cohesin dynamics sustains acute myeloid leukemia.

The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency.

Evaluating the Improvement of Blend Potency Measurements in the Feed Frame of a Rotary Tablet Press Using Combined NIR and Raman Spectroscopy.

This study investigated the added value of combining both near-infrared (NIR) and Raman spectroscopy into a single NIRaman Combi Fiber Probe for in-line blend potency determination in the feed frame of a rotary tablet press. A five-component platform formulation was used, containing acetylsalicylic acid as the Active Pharmaceutical Ingredient (API). Calibration models for the determination of 1 and 5% label claim tablets were developed using NIR and Raman spectra of powder blends ranging from 0.

Relevance of controlled cooling and freezing phases in T-cell cryopreservation.

When cells are cryopreserved, they go through a freezing process with several distinct phases (i.e., cooling until nucleation, ice nucleation, ice crystal growth and cooling to a final temperature).

A framework for the in silico assessment of the robustness of an MPC in a CDC line in function of process variability.

The shift from batch manufacturing towards continuous manufacturing for the production of oral solid dosages requires the development and implementation of process models and process control. Previous work focused mainly on developing deterministic models for the investigated system. Furthermore, the in silico tuning and analysis of a control strategy are mostly done based on deterministic models.

Cracking the code: Spatial heterogeneity as the missing piece for modeling granular fluidized bed drying.

Pharmaceutical twin-screw wet granulation is a multifaceted and intricate process pivotal to drug product development. Accurate modeling of this process is indispensable for optimizing manufacturing parameters and ensuring product quality. The fluid bed dryer, an integral component of this granulation process, significantly influences the granular critical quality attributes.

A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins.

In the field of drug discovery, understanding how small molecule drugs interact with cellular components is crucial. Our study introduces a novel methodology to uncover primary drug targets using andem ffinity urification for identification of rug-inding roteins (TAP-DBP). Central to our approach is the generation of a FLAG-hemagglutinin (HA)-tagged chimeric protein featuring the FKBP12(F36V) adaptor protein and the TurboID enzyme.

A Colourful Way to Unravel the Important Fluidization-Related Granule Size Effect on Semi-Continuous Drying.

Continuous twin screw wet granulation (TSWG) systems are possible pathways for oral solid dosage manufacturing in the pharmaceutical industry. TSWG requires a drying step after granulation before the tableting process. Typically, semi-continuous fluidized bed dryers (FBDs) are used for this purpose.

Analysis of the effect of formulation properties and process parameters on granule formation in twin-screw wet granulation.

In the last few years, twin-screw wet granulation (TSWG) has become one of the key continuous pharmaceutical unit operations. Despite the many studies that have been performed, only little is known about the effect of the starting material properties on the stepwise granule formation along the length of the twin-screw granulator (TSG) barrel. Hence, this study obtained a detailed understanding of the effect of formulation properties (i.

Validation of model-based design of experiments for continuous wet granulation and drying.

This paper presents an application case of model-based design of experiments for the continuous twin-screw wet granulation and fluid-bed drying sequence. The proposed framework consists of three previously developed models. Here, we are testing the applicability of previously published unit operation models in this specific part of the production line to a new active pharmaceutical ingredient.

T-shaped partial least squares for high-dosed new active pharmaceutical ingredients in continuous twin-screw wet granulation: Granule size prediction with limited material information.

This work presents a granule size prediction approach applicable to diverse formulations containing new active pharmaceutical ingredients (APIs) in continuous twin-screw wet granulation. The approach consists of a surrogate selection method to identify similar materials with new APIs and a T-shaped partial least squares (T-PLS) model for granule size prediction across varying formulations and process conditions. We devised a surrogate material selection method, employing a combination of linear pre-processing and nonlinear classification algorithms, which effectively identified suitable surrogates for new materials.

Mechanistic modeling of semicontinuous fluidized bed drying of pharmaceutical granules by incorporating single particle and bulk drying kinetics.

In this work, a mechanistic fluidized bed drying model computing the granule moisture content in function of granule size, drying time, process settings and formulation properties is developed. Modeling the moisture content distribution concerning the granule size is essential for tabletability and drug product quality. This work combines a mechanistic bulk model and a single-particle drying kinetics model in a semicontinuous mode.

Human neurotropic polyomavirus, JC virus, late coding region encodes a novel nuclear protein, ORF4, which targets the promyelocytic leukemia nuclear bodies (PML-NBs) and modulates their reorganization.

We previously reported the discovery and characterization of two novel proteins (ORF1 and ORF2) generated by the alternative splicing of the JC virus (JCV) late coding region. Here, we report the discovery and partial characterization of three additional novel ORFs from the same coding region, ORF3, ORF4 and ORF5, which potentially encode 70, 173 and 265 amino acid long proteins respectively. While ORF3 protein exhibits a uniform distribution pattern throughout the cells, we were unable to detect ORF5 expression.

Exploring experiences of times without care and encounters in dementia: protocol for a living and adaptive evidence map.

Introduction: Individuals with dementia spend most of the day without care, without encounters, and usually without activity. Although this has been proven in studies, there is a knowledge gap on how individuals with dementia experience these periods of time. Such knowledge would be highly relevant for health professionals and relatives to develop adequate strategies for dealing with these periods of time.

Development of Diclofenac Sodium 3D Printed Cylindrical and Tubular-Shaped Tablets through Hot Melt Extrusion and Fused Deposition Modelling Techniques.

The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME).

Effect of process parameters and formulation properties on the lead-lag between in-line NIR tablet press feed frame and off-line NIR tablet measurements.

The use of in-line near-infrared (NIR) measurements for tablet potency monitoring and diversion was studied. First, the optimal sample size for in-line NIR measurements inside the feed chute and the dosing and filling chamber of the tablet press feed frame was determined to allow proper comparison between these different measurement positions. Because of the considerably longer measurement time needed to obtain the same sample size inside the feed chute compared to the feed frame, the possibility of powder segregation inside the feed chute and the additional powder mixing inside the feed frame, the latter is preferred over the feed chute for in-line blend potency monitoring.